In Orch OR model ; using electromagnetic fields, the brain captures, stores and analyzes the information of the cells and then sends the necessary commands to them. If the cells undergo changes and become cancer cells, the information stored in the brain and the electromagnetic signals inside and outside it change. Based on these changes, tumor and cancer formation can be detected in the early stages, and by storing the right information in the brain; it created the context for sending appropriate messages to return the cells to a normal state.

We present the case of a 35-year-old male with first degree family history of gastric cancer (father diagnosed at the age of 45), that was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Mesothelioma of the peritoneum is the second most prevalent type. The peritoneum, the membrane lining the abdomen and abdominal organs, is affected in this type of cancer. A common risk factor is exposure to asbestos. There isn’t a cure, but surgery, chemotherapy, and palliative care can improve your prognosis and quality of life. Here we present a case of a 47-year-old female with peritoneal mesothelioma.

Abstract The number of non-melanoma skin cancers (NMSC) removed from Australians is increasing every year. The number of deaths from NMSC is increasing but so is the population. However, the population has greatly changed with many people at low risk for skin cancer migrating to Australia. The death rate from NMSC for the entire population and susceptible populations since 1971 is examined in this article. Materials and methods Data on the Australian population was obtained from the Australian Bureau of Statistics (ABS). Every five years a census is held in Australia and detailed information of the population is provided. The ABS also provided yearly data on the causes of death in Australia. Results The total population increased from 12,755,638 in 1971 to 25,738,140 in 2021. However, the susceptible population increased by far less, from 12,493,780 to 19,773,783. The number of deaths from NMSC increased from 143 to 765. The crude death rate for the susceptible population increased for 1.1 per 100,000 to 3.9 per 100,000. The crude death rate in the susceptible population aged 65 or more increased from 9.4 to 18.2 per 100,000. Conclusion Deaths from NMSC are increasing despite public health campaigns to prevent skin cancer. On current trends, NMSC will cause more deaths than melanoma in Australia.

The Fractal Analysis of Medical Images is an investigation field in those that numerous results of important value have been obtained. This work describes the basic foundations of the Fractal Analysis and its application has more than enough medical images, leaning on in five scientific investigations.

N6-methyladenosine (m6A) is an RNA modification wherein N6-position of adenosine is methylated. It is one of the most prevalent internal modifications on RNA and regulates various aspects of RNA metabolism. M6A is deposited by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which modulate splicing, export, translation and stability of the modified mRNA. Recently evidence suggests that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), circular RNAs (circRNAs), and long con-coding RNAs (lncRNAs) are also targeted by this modification. Depending on the ncRNA species, m6A may affect processing, stability, or localization of these molecules. The m6A modified ncRNAs are implicated in a number of diseases including cancer. In this review, I summarize the role of m6A modification in the regulation and function of ncRNAs in tumor development. Moreover, the potential applications in cancer prognosis and therapeutics is discussed.

Histone modifications, especially H3K27 and H3K36 methylations, are crucial for epigenetic regulation and are often dysregulated in cancer. In a comprehensive analysis of 11,194 patient samples across 32 cancer types, we identified significant genomic alterations in H3K27 and H3K36 modifiers, with the most common being in KDM6B, BRPF1, KDM6A, SETD2, and NSD1. Patients with these alterations also frequently exhibited mutations in genes like TP53 and PIK3CA. Moreover, the presence of these histone modifier alterations correlated with poorer overall survival, emphasizing their potential as both oncogenic drivers and prognostic markers in various cancers.

Comprehensive studies into the various causes of this ubiquitous disease have been prompted by the worldwide increase in cancer incidence. There are many potential causes of cancer, but environmental factors are of particular concern now. This abstract explores the complex link between environmental factors and the growing cancer epidemic, shedding light on the role that our immediate environment plays in the emergence of cancers. The environment can contain carcinogenic agents that gradually influence the course of cancer, including air pollutants, water contaminants, workplace exposures, and industrial activities. The ways through which environmental carcinogens may cause DNA damage and unchecked cell proliferation are discussed in this abstract. Environmental justice and the moral necessity to reduce inequities in exposure and health effects are highlighted to underline the disproportionate impact on vulnerable groups. The study presented here highlights the need for preemptive action to reduce environmental risks. Society can reduce the hidden threat posed by environmental carcinogens through strict legislation, sustainable practices, and community-driven initiatives. In order to lessen the cancer burden and secure a healthier future for all, the authors of this abstract argue that there must be a concerted effort to create surroundings that promote health and well-being.

Background: The interruption of the activity of the population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at di-agnosis in a CRC screening program. Methods: We analyzed all the invitations between January 1, 2019, and December 31, 2021. We defined the pandemic period as the period after March 12, 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically CRC and colorectal neoplasia (CRC and/or adenoma), as well as CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% pandemic), 439,687 FIT were returned (62.4% pandemic) and 23,092 colonoscopies were performed (59.1% pandemic). Colon-oscopies were normal in 7,378 subjects (32.4%) and a CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly seven months during the pandemic period (p<0.001). In all the invitations, the delay from the invitation to the colonoscopy increased sig-nificantly by 8 days (p<0.001). Once adjusted for the confounding variables, participation in the screening program increased significantly (OR=1.1; 95% CI=1.09-1.11), with no changes in the adherence to colonoscopy (OR=0.9; 95% CI=0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR=0.90; 95% CI=0.78-1.02) or colorectal neoplasia (OR=0.98; 95% CI=0.92-1.03) detection. Finally, we found no differences in CRC stage at diagnosis (p=0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pan-demic increased the delays, it did not reduce participation, adherence to colonoscopy, or the di-agnostic yield of colonoscopy.

Abstract: Background and Objectives: A growing number of epidemiologic studies have found that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in pro-inflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia, and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of CEA, CRP, serum albumin level, hemoglobin, and LDH as biomarkers for cancer risk and the biological implications of diabetes on the evolution and prognosis of oncological patients. Material and methods: We conducted a retrospective, longitudinal, observational study, on a total group of 434 patients, 217 diagnosed with a form of cancer and with type 2 diabetes as a comorbidity, and the other 217 – control group, without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type 2 diabetes and cancer. Conclusions: The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug. Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. Additionally, the interplay between hereditary variations and acquired mutations in the EGFR pathway remains unknown. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic effectiveness, considering their interaction with the EGFR pathway mutations. In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1 and MTHFR polymorphisms are independent indicators of a poor prognostic, irrespective of EGFR pathway mutations. BRAF V600E wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYD rs1801265, ABCB1 rs1045642 and MTHFR rs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of EGFR pathway mutations.

Backgound: Exosomes are extracellular nanovesicles, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in case of tumorigenesis, opens different scenarios on the possible application in the research for new biomarkers.Methods: The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA) and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, determining an increase in labor time and costs. Results: The analysis of PSA-expressing exosomes provides an incredibly accurate way to discriminate between healthy patients and those with prostate disease. Specifically, IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH).An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy control. Conclusions: The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease, However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for a large-scale use.

Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

Cancer is the most feared disease, with more than 1.6 million cases each year. Cancer can start almost anywhere in the human body, from the uncontrollable growth and multiplication of damaged cells. Cancerous tumors can spread into the human body (a process called metastasis) as a solid form usually, but the cancers of blood generally do not. Cancer treatment includes chemotherapy, surgery and radiations. In this article we will address inorganic compounds as a source of treatment, diagnosis, carriers of active substances.

Selectins are responsible for the early stages of cell migration as they control cell adhesion. They make the microenvironment permissive for metastatic events by promoting the activation of other cell adhesion molecules (CAMs). We employed several robust bioinformatics tools to evaluate gene sequence; single nucleotide polymorphisms (SNPs) in intronic and UTR regions; and missense SNPs with amino acid change in L-selectin (SELL), E-selectin (SELE), P-selectin (SELP) and PSGL-1 (SELPLG). We demonstrated that gene polymorphisms rs2229569, rs1131498, rs4987360, rs4987301 and rs2205849; polymorphisms rs3917777, rs2205894 and rs2205893 of SELP gene; rs7138370, rs7300972 and rs2228315 variants of SELPLG gene; and rs1534904 and rs5368 polymorphisms of SELE gene may produce important alterations in the DNA structure and consequent alterations in the morphology and function of the corresponding proteins. These Selectin polymorphic variants deserve further investigation in cancer patients, as they may become useful clinical markers for risk determination, diagnostic and prognostic biomarkers or even targets for targeted therapies.

Background: Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease has been shown to be related to insulin resistance and multiplied blood sugar ranges. Further, it has been found that the use of metformin improves the menstrual cycles and ovulation rates of these women. Methods: A structured questionnaire will be conducted to determine the prevalence of breast cancer among women using metformin in the Ha’il region. Result: Incidence of breast cancer among women using metformin in the Ha’il region is very low. Conclusions: According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study have corroborated the literature for the same by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER, Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures, with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.

Background: Oncology patients experience a large number of symptoms and, those referring to cognitive performance has an ever-increasing importance in clinical practice due to the increase in survival rates and interest in the patient's quality of life. The studies reviewed show that chemotherapy-related cognitive impairment may occur in 15 and 50% of oncology patients. The main objective of this research was to study the impact of chemotherapy on the cognitive function of patients with locoregional breast cancer.Method: Analytical, prospective, longitudinal study using three measures, unifactorial intrasubject design, non-probability and random selection sampling. The sample comprised women newly diagnosed with locoregional breast cancer in stages I, II, IIIA who received chemotherapy at the University Hospital of Salamanca (Complejo Asistencial Universitario de Salamanca) randomly selected for three years. Semi-structured interviews were conducted, and anxiety and depression (Hospital Anxiety and Depression scale, HAD); quality of life (QLQ-BR23 scale) and the following cognitive variables were assessed: processing speed, attention, memory and executive functions (subtests of the Wechsler Intelligence Scale and the Trail Making Test). Results: The final sample size included 151 participants; 23 were excluded. A decline in cognitive performance was observed in patients which was not completely recovered two months after chemotherapy had been completed. Also, worse cognitive performance was observed in patients with anxious or depressive symptoms. There is a negative impact on the quality of life. Conclusion: Chemotherapy has an impact on the cognitive performance of oncology patients in most of the cognitive domains studied.

Background: ethical issues that arise during the care of a pregnant woman with cancer are challenging to physicians, policymakers, lawyers, and the bioethics community. This article is restricted to a discussion of ethical dilemmas and controversial case reports, mainly focused before the third trimester of pregnancy, when a conflict could exist between cancer and pregnancy outcomes.Methods: published literature was retrieved through searches in PubMed or Medline, CINAHL, the Cochrane and Google Academic in April 2020, using appropriate controlled keywords (cancer, neoplasm, pregnancy, ethics). Results were restricted to review articles, ethical perspectives, clinical practice guidelines and case-based teaching guides.Discussion: when a conflict arises in the maternal-foetus dyad, like the one related with cancer treatment and the risk of foetal demise, a range of ethical frameworks might be useful to consider in the decision-making process. Pragmatic theoretical approaches include case-based analysis, ethics of care, feminist theory, and traditional ethical principlism using the framework of autonomy, beneficence, non-maleficence, and justice. Also, societal and practitioner values could add value and an ethics consultation may be helpful to mediate conflict resolution. The physician must balance autonomy and beneficence-based obligations to the pregnant woman with cancer, along with beneficence-based obligations to the foetus.Conclusions: ethical challenges have received less attention in the literature, particularly before the third trimester of pregnancy. Best, unbiased and balanced information must be granted both to the patient and to the family, regarding the benefits and harms for the woman herself as well as for the foetal outcome.

With the continuous progress in modern medicine, the early detection rate of gastric cancer has increased, and the mortality rate has decreased. However, gastric cancer remains the third leading cause of cancer-related death worldwide, with a high recurrence rate. Metastasis is the leading cause of death and recurrence of gastric cancer, which greatly hinders treatment success. Cancer development is a complex process involving multiple sequential steps. In the metastatic cascade, local invasion may be considered an initial, crucial step in the development of a malignant tumor, which leads to distant metastasis. Epithelial-mesenchymal transformation (EMT) is one of the most important developmental processes that occur during tumor invasion. EMT confers certain basic abilities to cancer cells, such as migration, invasion and anti-apoptotic ability, thus initiating and increasing metastasis. However, little is known about the molecular mechanisms that promote EMT and gastric cancer cell metastasis. A number of recent studies have found that circular RNAs（circRNAs）are associated with gastric cancer EMT, regulating the EMT process and promoting the occurrence and development of tumors. Because of their unique continuous circular structure, circRNAs have relatively high stability in plasma and cells, making them more suitable as diagnostic biomarkers in malignant tumors. Therefore, understanding the mechanism of circRNAs in EMT in gastric cancer is an important research direction to actively prevent tumor metastasis and improve the therapeutic effect on advanced malignant tumors.

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

With the advancement of next generation sequencing in past several years, a rising number of non-coding RNAs have been found as new actors to regulate gene expression. Non-coding RNAs not only play important roles in carcinogenesis, but also affect the clinical treatment strategies. They have been proved to be deeply correlated with chemoresistance in several cancers. Ovarian cancer is the leading cause of death in gynecological malignancy, with low 5-year survival rate. Most patients are identified when they have late-stage disease. This review mainly makes a compilation of the most relevant research literature in this field with the purpose of shedding light on the relation between ncRNAs and chemoresistance in ovarian cancer.

Purpose: Early glottic cancer is a highly curable malignancy. Disease control is achieved by resec-tion or external beam radiation with similar long-term results according survival. Surgery is predominantly performed by transoral endoscopic approach, due to reduced complication rates when compared to open cordectomy. Open cordectomy might still be warranted in cases of inad-equate surgical accessibility. Aim of the present study was to compare endoscopic versus open approach in relation to complications and outcome in an up-to-date patient group. Methods: 219 patients underwent primary tumor resection in early glottic cancer (UICC stages I-II). 168 opera-tions were performed endoscopically, 51 operations were open transcervical cordectomies. We compared survival data with non-parametric methods and functional outcome according to need of tracheostomy, feeding tube and voice functional outcome following ELS protocol. Results: There were no significant differences in overall survival (OS). 2 years OS after endoscopic surgery was 90.5% vs 95.3% after transcervical resection. As expected, OS in T1b and T2 tumors was worse than in T1a tumors. We found a statistically significant difference in disease free survival (DFS) within the T1a and T1b/T2 group (Log rank test: p=0.006) but no relevant difference be-tween the two surgical modalities, even when the data was stratified by T-categories performing a Cox regression (hazard ratio 1.21, p=0.712). Patients who underwent open surgery had a sig-nificantly worse peri- and postoperative course with longer hospital stay, higher frequency of tracheotomies and longer need for nasogastric tubes. Functional results were comparable within the two patient groups while higher tumor size / stage was an unfavorable predictor for voice re-habilitation. Conclusion: Open cordectomy leads to more complications but offers comparable oncological and functional outcome when compared to transoral endoscopic approach in early glottic cancer. Open surgery therefore continues to be a valid treatment option when endoscopic resection is not possible.

Background: Sexual dysfunction is the most common side effect encountered by cervical cancer patients during and after treatment, and rehabilitation strategies are needed to improve their quality of life. A variety of rehabilitation strategies have been reported in previous studies, varying by country, race and even continent. However, the common rehabilitation strategies used by cervical cancer survivors in Tanzania and their outcomes are unknown. The study aimed to unfold sexual rehabilitation strategies and outcome practiced by cervical cancer survivors who experienced sexual dysfunction during and after treatment in North-western Tanzania. Methods: Descriptive qualitative study were employed. Phenomenology study design used with a sample of 7 participants and data corrected via in-depth interview guided by 11 questions. Audiotaped and transcribed to get main themes and sub themes through deductive analysis. Results: Most participants reported inability to achieve an orgasm and low libido and dyspareunia after treatment. Most participants were eagerly to have their sexual activity recovered. However, they were not familiar with any rehabilitation strategy after the experience of sexual dysfunction. Even though, some of the participants attempted various interventions, but all were unsatisfactory leading to a significant decline in sexual interest and activity. Conclusion: Cervical cancer survivors are not familiar with any sexual rehabilitation strategies. Health education concerning various sexual rehabilitation strategies should be provided to survivors during and even after treatment.

Tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cell, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs are crucial for enhancing the treatment outcome and reducing the burden of toxicity. In this review, we provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we have dissected the signalling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancement in role of various splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSCs enhancement, immunomodulation, metastasis, chemoresistance, metabolic reprogramming and further suggest that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

Background: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. Methods: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network : Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. Results: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. This data originates from their electronic medical records, encompassing about 65 millions of medical records. Thanks to the structured data, which is harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. Conclusions: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance to regulations and acceleration of cancer research projects.

Background. This study aimed to establish a prognostic nomogram for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with early-onset endometrial cancer (EOEC). Methods. Patients diagnosed with EOEC during 2004-2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were performed to ascertain the independent factors impacting the prognosis of EOEC patients, while a prognostic nomogram was established. Its performance was verified by the receiver operating characteristic (ROC) curves, and calibration plots. The prediction accuracy and clinical net benefit between the model, TNM stage and SEER stage were further compared by the concordance index (C-index) and decision curve analysis (DCA). Results. A total of 4415 eligible patients with EOEC were identified and enrolled in this study. Independent prognostic factors for OS and CSS were confirmed by multivariate Cox regression, which were further incorporated to constructed a nomogram. ROC curves and calibration curves indicated an optimal accuracy of the nomogram. Meanwhile, the C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Conclusions. Nomogram based on risk factors was developed as an individualized tool to predict OS and CSS for EOEC patients. The novel tool will assist in patient counseling and selection of appropriate therapeutic regimens.

Since decades, oxybutynin hydrochloride is prescribed to improve bladder control in cases of incontinence and excessive urination frequency. This review summarizes synthetic methods enabling preparation of the racemic drug and, in a detailed manner, preparation of (S)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid, a key intermediate in the synthesis of (S)-oxybutynin. Mode of action and metabolism are briefly commented in order to explain the main adverse effects associated with its use and to justify the evolution observed in the diverse commercial formulations. Repositioning opportunities are discussed in terms of clinical trials for the management of hyperhidrosis, hot flashes, and obstructive sleep apnea.

Abstract: The ability to detect several types of cancer using a non-invasive, blood-based test holds the potential to revolutionize oncology screening. We mined tumor methylation array data from the Cancer Genome Atlas (TCGA) covering 14 cancer types and identified two novel, broadly oc-curring methylation markers at TLX1 and GALR1. To evaluate their performance as a general-ized blood-based screening approach, along with our previously reported methylation bi-omarker, ZNF154, we rigorously assessed each marker individually or combined. Utilizing the TCGA methylation data and applying logistic regression models within each individual cancer type, we found that the three-marker combination significantly increased the average area under the ROC curve (AUC) across the 14 tumor types compared to single markers (p= 1.158e-10; Friedman test). Furthermore, we simulated dilutions of tumor DNA into healthy blood cell DNA and demonstrated increased AUC of combined markers across all dilution levels. Finally, we evaluated assay performance in bisulfite sequenced DNA from patient tumors and plasma, in-cluding early-stage samples. When combining all three markers the assay achieved 100% sensi-tivity and specificity, as demonstrated in lung cancer plasma samples. In patient plasma from hepatocellular carcinoma, ZNF154 alone yielded the highest combined sensitivity and specificity values averaging 68% and 72%, whereas multiple markers could achieve higher sensitivity or specificity, but not both. Altogether this study presents a comprehensive pipeline for the identifi-cation, testing and validation of multi-cancer methylation biomarkers with a considerable poten-tial for detecting a broad range of cancer types in patient blood samples.

The study of notable people as agents for increasing cancer awareness started just in the last decades of the 20th century. This study aimed to identify Pan-American notable people with head and neck cancer (HNC) and to assess HNC’s professional perspective on communicating stories of notable patients with HNC to promote prevention. Methods: This cross-sectional study was conducted by applying a RedCap questionnaire to oral medicinists, oral pathologists, head and neck surgeons, and clinical oncologists with experience in HNC research, education, or treatment in Pan-American countries. Additionally, a structured search was performed on PubMed, Scopus, EMBASE, Web of Science, LILACS, and gray literature Results: We identified 42 notable people from the United States, Brazil, Argentina, Mexico, El Salvador, Chile, Colombia, and Peru who were mainly actors, athletes, and musicians. Participants agreed that stories of notable patients with HNC can positively impact the population and promote prevention if communicated by the internet, social media, and television. Conclusion: In the Pan-American region, notable individuals who have suffered from HNC may be powerful advocates for increasing cancer awareness and promoting prevention strategies. The professionals involved in the study expressed a positive inclination towards using the stories of these notable HNC survivors as an effective prevention strategy.

There is rapidly emerging evidence from pre-clinical studies, patient samples and patient subpopulations that certain chemotherapeutics inadvertently produce prometastatic effects. Prior to this, we showed that doxorubicin and daunorubicin, stiffen cells before causing cell death, predisposing the cells to clogging and extravasation, the latter being a step in metastasis. Here, we investigate which other anti-cancer drugs might have similar prometastatic effects by altering the biophysical properties of cells. We treat myelogenous (K562) leukemic cancer cells with the drugs nocodazole and hydroxyurea, and then measure their mechanical properties using the microfluidic microcirculation mimetic (MMM) device, which mimics aspects of blood circulation and enables the measurement of cell mechanical properties via transit times through the device. We also quantify the morphological properties of cells to explore biophysical mechanisms underlying the MMM results. Results from MMM measurements show that nocodazole- and hydroxyurea-treated K562 cells exhibit significantly altered transit times. Nocodazole caused significant (p &lt; 0.01) increase in transit times, implying a stiffening of cells. This work shows the feasibility of using the MMM to explore possible biophysical mechanisms that might contribute to chemotherapy-induced metastasis. Our work also suggests cell mechanics as a therapeutic target for much needed antimetastatic strategies in general.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.

The Herpes Virus Entry Mediator (HVEM) delivers a negative signal to T cells mainly through the B and T Lymphocyte Attenuator (BTLA) molecule and thus, could represent a novel immune checkpoint during an anti-tumor immune response. A formal demonstration that HVEM can be targeted for cancer immunotherapy is however still lacking. Here, we first show that HVEM and BTLA were associated to a worse prognosis in patients with prostate adenocarcinomas, indicating a detrimental role for this pair of molecule during prostate cancer progression. We then show that a monoclonal antibody to human HVEM significantly impacted the growth of a prostate cancer cell line in immuno-compromised NOD.SCID.gc-null mice reconstituted with human T cells. Using CRISPR/Cas9, we showed that HVEM expression by the tumor was mandatory to observe the therapeutic effect. Mechanistically, tumor control was dependent on CD8+ T cells and was associated to an increase in the proliferation and number of tumor-infiltrating leukocytes. Accordingly, the expression of genes belonging to various T cell activation pathways were enriched in tumor infiltrating leukocytes, whereas genes associated with immuno-suppressive pathways were decreased, possibly resulting in modifications of leukocyte adhesion and motility. Finally, we developed a simple in vivo assay in humanized mice to directly demonstrate that HVEM was an immune checkpoint for T-cell mediated tumor control. Our results show that targeting HVEM is a promising strategy for prostate cancer immunotherapy.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Intermediate filaments constitute the third component of the cellular skeleton. Unlike actin and microtubule cytoskeletons, the intermediate filaments are composed of wide variety of structurally related proteins showing distinct expression patterns in tissues and cell types. Changes in expression patterns of intermediate filaments are often associated with cancer progression, in particular with phenotypes leading to increased cellular migration and invasion. In this review we will describe the role of vimentin intermediate filaments in cancer cell migration, cell adhesion structures, and metastasis formation. The potential for targeting vimentin in cancer treatment and the development of drugs targeting vimentin will be reviewed.

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on the tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer, and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be up-regulated in multiple cancer types. In this study, EphaA2 and EphB4 are evaluated as target for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be an especially promising candidate for IGOS of colorectal cancer.

Extremely low-frequency electromagnetic fields (ELF-EMFs) are non-ionizing radiations typically emitted by power lines, electrical wiring and electrical appliances. Epidemiological studies have repeatedly shown a positive association between ELF-EMFs and childhood leukemia. Exposures greater than 0.3-0.4 µT increase the risk by approximately 1.5-2 fold, and estimates indicate that up to 2% of childhood leukemia cases in Europe may be attributable to ELF-EMFs. However, it is considered unlikely that ELF-EMFs can cause cancer, because carcinogenesis requires the accumulation of DNA alterations and ELF-EMFs do not have enough energy to damage the DNA. Lack of biological plausibility is a barrier to accept the evidence of carcinogenicity in human studies and to take measures to protect pregnant women and children from ELF-EMFs. Recent evidence indicates that non-mutagenic agents can cause DNA alterations and increase the risk of cancer by promoting the accumulation of cell divisions in stem cells. Cell division generates DNA alterations (e.g., mutations arising during DNA replication), which occur even in the absence of DNA-damaging agents. Importantly, ELF-EMFs can trigger the division of stem cells; this effect is under development in the field of regenerative medicine. A possible mechanism by which ELF-EMFs induce the malignant transformation of hematopoietic stem cells is discussed.

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85-90Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemotherapy (total dose 60-65Gy at point A), followed by surgery which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated patients compared to 62% for non-operated patients receiving suboptimal concurrent chemotherapy alone. In conclusion, In Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control.

ABSTRACT Background It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under- or over-treatment. Deep Neural Network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tunning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15-years after the initial treatment. We developed DNN models as well as models using 9 other machine learning methods including Naive Bayes (NB), Logistic Regression (LR), Support Vector Machine (SVM), LASSO, Decision Tree (DT), k-Nearest Neighbors (KNN), Random Forrest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared the deep learning models to the models trained using the 9 other machine learning methods. Results Based on the mean test AUC results, DNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM respectively, out of 10 machine learning methods. The top performing methods in predicting 5-year BCM are XGB(1^st), RF(2^nd), and KNN(3^rd). For predicting 10-year BCM the top performers are XGB (1^st), RF(2^nd), and NB(3^rd) . Finally, for 15-year BCM the top performers are SVM (1^st), LR and LASSO (tied for 2^nd), and DNN (3^rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05 DNN overall performs no worse than other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods such as XGB, RF, and SVM are very strong competitors of DNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DNN is way more than that required to do grid search with the other 9 machine learning methods.

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of unavoidable mutations in driver genes. However, no correlation between the number of gene mutations and cancer risk across tissues has been reported. Because many somatic mutations in cancers originate prior to tumor initiation and the number of cell divisions occurring during tumor growth is similar among tissues, here I use whole genome sequencing information from 22,086 cancer samples and incidence data from the largest cancer registry in each continent to study the relationship between the number of gene mutations and the risk of cancer across 33 tissue types. Results show a weak positive correlation (mean = 0.14) between these two parameters in each of the five cancer registries. The correlation became stronger (mean = 0.50) when gender-related cancers were excluded. Results also show that 1,003 samples from 29 cancer types have zero mutations in genes. These data suggest that cancer etiology can be better explained by the accumulation of stem cell divisions than by the accumulation of gene mutations. Possible mechanisms by which the accumulation of cell divisions in stem cells increases the risk of cancer are discussed.

Lung and colon cancers are among the leading causes of cancer-related mortality worldwide. Early and accurate detection of these cancers is crucial for effective treatment and improved patient outcomes. False or incorrect detection is more harmful. Accurately detecting cancer in a patient's tissue is crucial to their effective treatment. While analyzing tissue samples is complicated and time-consuming, deep learning techniques have made it possible to complete this process more efficiently and accurately. As a result, researchers can study more patients in a shorter amount of time and at a lower cost. Much research has been conducted to investigate deep learning models that require great computational ability and resources. However, None of these have had a 100% accurate detection rate for these life-threatening malignancies. Misclassified or falsely detecting cancer can have more harmful consequences. This research proposes a new lightweight, parameter-efficient, and mobile-embedded deep learning model based on a 1D convolutional neural network with Squeeze-and-Excitation layers for efficient lung and colon cancer detection. This proposed model diagnoses and classifies lung squamous cell carcinomas and adenocarcinoma of the lung and colon from digital pathology images. Extensive experiment demonstrates that our proposed model achieves 100% accuracy for detecting lung, colon, and lung and colon cancers from the histopathological (LC25000) lung and colon datasets, which is considered the best accuracy for around 0.35 million trainable parameters and around 6.4 million flops. Compared with the existing results, our proposed architecture shows state-of-the-art performance in lung, colon, and lung and colon cancer detection.

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

Background. One of the most important prognostic factors in periampullary and pancreatic cancers is perineural infiltration, whose preoperative detection could be decisive in selecting which patients should not undergo upfront surgery. We evaluated CA 19.9 and the Neutrophil-to-lymphocyte ratio (NLR) as preoperative predictors of perineural invasion (PNI). Methods: Retrospective analysis including patients with periampullary and pancreatic cancers who underwent curative resection from January 2013 to August 2023 in our institution. A univariate analysis and multivariate analysis were performed to analyze the association between the CA 19.9 and NLR with the existence of PNI. Results: A total of 136 patients were included in the study. PNI was observed in 95 (69.9%) patients. The selected cut-off points were NLR: 2.2 and CA 19.9: 37 U/mL. In univariate analysis, NLR (p=0.001) and CA 19.9 (p=0.006) were statistically significantly associated with PNI. In multivariate analysis, baseline NLR levels (p=0.012; OR: 1.95; 95%CI: 1.16-3.29) as well as CA 19.9 levels (p=0.026; OR: 1.67; 95%CI: 1.06-2.64) remained independent prognostic factors for PNI. The area under de ROC curves was 0.67 for CA 19.9 (p=0.004) and 0.72 for NLR (p<0.001). A sensitivity of 65.9% with a positive predictive value of 81.7% were obtained for CA 19.9, and a sensitivity of 62.1% with a positive predictive value of 84.3% were achieved for NLR. Conclusion: Preoperative CA 19.9 and NLR levels seem to be good predictors of PNI. In patients with normal levels of CA 19.9, preoperative NLR above of 2.2 should be an indication for neoadjuvant therapy.

Background: Cancer-Related Fatigue (CRF) is a prevalent and debilitating symptom in breast cancer patients, significantly impacting their quality of life and potentially affecting postoperative outcomes. Despite advances in breast cancer treatment, the long-term implications of CRF on prognosis remain unclear. Methods: This retrospective cohort study included 310 postoperative breast cancer patients from two large comprehensive hospitals. We systematically collected demographic, medical history, lifestyle, psychological status, and CRF data. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Random forest survival analysis, propensity score matching, Kaplan-Meier survival analysis, and restricted cubic spline analysis were utilized to comprehensively evaluate the relationship between CRF and postoperative prognosis. Results: Higher CRF scores were associated with worse postoperative outcomes (HR = 1.07, 95% CI: 1.03-1.10, P < 0.001). Other independent prognostic factors included higher HADS scores (HR = 1.09, 95% CI: 1.01-1.17, P = 0.032), not undergoing breast-conserving surgery (HR = 0.43, 95% CI: 0.20-0.89, P = 0.024), and not receiving endocrine therapy (HR = 7.13, 95% CI: 2.64-19.22, P < 0.001). Random forest survival analysis highlighted CRF as the most critical variable impacting prognosis. Propensity score matching effectively balanced baseline characteristics, and Kaplan-Meier survival curves demonstrated significantly lower survival rates in high-CRF patients both before and after matching (P < 0.05). Restricted cubic spline analysis revealed a nonlinear relationship between CRF scores and disease progression risk, with significant risk increases beyond specific thresholds. Conclusions: CRF is a crucial predictor of disease progression in postoperative breast cancer patients. Higher CRF and HADS scores, non-breast-conserving surgery, and lack of endocrine therapy are associated with poorer prognosis. These findings underscore the importance of comprehensive postoperative care, including effective management of fatigue and psychological health, to improve patient outcomes. Future research should focus on prospective studies and targeted interventions for CRF to validate these findings and enhance clinical practices.

Background: The incidence of various types of cancer, for example papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diag-nostic biomarkers must be identified and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs sus-pected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis along with identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulat-ing blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, miR-1, miR-206, and miR-221, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG), and from the culture medium of a PTC cell line (MDAT32) and were duly characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes were associated to the molecular pathogenesis of PTC. Conclusions: Thus, our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.

Purpose: To simplify the application of optical coherence tomography (OCT) for examination of subsurface morphology in the oral cavity and reduce barriers towards adoption of OCT as a biopsy guidance device. The aim of this work was to develop automated software tools for simplified analysis of the large volume of data collected during OCT. Methods: Imaging and corresponding histopathology were acquired in-clinic using a wide-field endoscopic OCT system. An annotated dataset (n = 294 images) from 60 patients (34 male, 26 female) was assembled to train four unique neural networks. A deep learning pipeline was built using convolutional and modified u-net models to detect the imaging field of view (network 1), detect artifacts (network 2), identify the tissue surface (network 3), and identify the presence and location of the basement membrane (network 4). Results: The area under the curve of the image and artifact detection networks was 1.00 and 0.94 respectively. The Dice similarity score for the surface and basement membrane segmentation networks was 0.98 and 0.83 respectively. Conclusion: Deep Learning (DL) techniques can identify the location and variations in the epithelial surface and basement membrane in OCT images of the oral mucosa. Segmentation results can be synthesized into accessible en face maps to allow easier visualization of changes.

Objective: The aim of our study was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Results: There was a statistically significant age difference between the two study periods, both by the average age of patients and by age group. The mean difference was 32 years before the pan-demic and 35 years during the pandemic (p-value >0.05). The majority of patients presenting for investigations before and during the pandemic were in the 30-39-year-old age group (31.95%, respectively; 34.2% (p-value = 0.003). The biggest patient loss ratio identified by age group was in the 50–59 years: 14,53% in the pre-pandemic period and 9,1% in the pandemic period. In the pan-demic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the prepandemic period, with an increase in more severe lesions in the pandemic period, has a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusion: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervicorrhagia as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in associate with other head and neck cancers. Archived tumour tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, P = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, P = 0.006), but no significant difference between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer managrement. Recent findings highlight the significance of microbial alterations in tissues, such as the gut and the breast, and their role in influencing breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, strategic manipulation of the microbiome and its metabolites presents innovative prospects for enhancing cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

There are compelling evidences that the immune system is to confer protection not only against foreign pathogens but also against cancer. But if the immune system can’t detect every malignant cell, and at the same time a suitable tumor microenvironment (TME) is formed by inflammatory processes, a carcinogenesis is not longer to be blocked. Once the tumor cells have found their niche, the tumor cells are trained by immune cells turned inside out in how to deal with the immune system "out there". The TME is a training camp and protected space for tumor cells. The Corona crisis has revived a therapeutic approach that was thought to be almost dead: RNA vaccines. Despite decades of research and many clinical studies, no registered RNA cancer vaccine exists today. But the SARS-CoV-2 RNA vaccines against COVID-19 disease have demonstrated their dangerous weaknesses. RNA vaccines manipulate the innate immunity and make the body susceptible to any viral infection. There is also the possibility of integration into the genome. The few approved therapeutic cancer vaccines show little effect. Despite some successes, immunotherapies remain ineffective for most patients with cancer. Powerful therapeutic cancer vaccines remain an unfulfilled dream, a misconception.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs &gt; 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

More than 1 million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at late stage, either because lack of symptoms such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV) whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer. uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404) a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

Seemingly normal tissues progressively become populated by mutant clones over time. Most of these clones bear mutations in well-known cancer genes but only rarely do they transform into cancer. This poses questions on what triggers cancer initiation and what implications somatic variation has for cancer early detection. We analysed recent mutational screens of healthy and cancer-free diseased tissues to compare somatic drivers and the causes of somatic variation across tissues. We then reviewed the mechanisms of clonal expansion and their relationships with age and diseases other than cancer. We finally discussed the relevance of somatic variation for cancer initiation and how it can help or hinder cancer detection and prevention. The extent of somatic variation is highly variable across tissues and depends on intrinsic features, such as tissue architecture and turnover, as well as the exposure to endogenous and exogenous insults. Most somatic mutations driving clone expansion are tissue-specific and inactivate tumour suppressor genes involved in chromatin modification and cell growth signalling. Some of these genes are more frequently mutated in normal tissues than cancer, indicating a context-dependent cancer promoting or protective role. Mutant clones can persist over a long time or disappear rapidly, suggesting that their fitness depends on the dynamic equilibrium with the environment. The disruption of this equilibrium is likely responsible for their transformation into malignant clones and knowing what triggers this process is key for cancer prevention and early detection. Somatic variation should be considered in liquid biopsy, where it may contribute cancer-independent mutations, and in the identification of cancer drivers, since not all mutated genes favouring clonal expansion also drive tumourigenesis. Somatic variation and the factors governing homeostasis of normal tissues should be taken into account when devising strategies for cancer prevention and early detection.

Dehydrodiisoeugenol (DEH), a novel lignan component extracted from the Nutmeg seeds, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anti-cancer activity in gastrointestinal cancer is still to be investigated. Here, the anti-cancer effect of DEH to human colorectal cancer and its underlying mechanism were evaluated. The DEH treatment arrests the cell cycle of colorectal cancer cells at G1/S phase, which leading to a significant cell growth inhibition. Moreover, it can induce strong cellular autophagy and the autophagy would be inhibited through autophagic inhibitors with reducing EDH-induced inhibition of cell growth in colorectal cancer cells. Further studies indicated that DEH can also induce endoplasmic reticulum (ER) stress, and could subsequently stimulating autophagy through activating PERK/eIF2α and IRE1α/XBP-1s/CHOP pathways. Knockdown of PERK or IRE1α can significantly decrease the DEH-induced autophagy and retrieve cell viability in cells treated with DEH. What’s more, DEH exhibits significant anti-cancer activities through CDX- and PDX-model as well. Taken together, our studies strongly suggest that DEH might be a potential anti-cancer agent against colorectal cancer via activating ER stress-induced autophagy inhibition.

In Taiwan, colorectal cancer is ranked second and third in terms of mortality and cancer incidence, respectively. In addition, medical expenditures related to colorectal cancer are considered to be the third highest. While advances in treatment strategies have provided cancer patients with longer survival, potentially harmful second primary cancers can occur. Therefore, second primary colorectal cancer analysis is an important issue with regard to clinical management. In this study, a novel predictive scheme was developed for predicting the risk factors associated with second colorectal cancer in patients with colorectal cancer by integrating five data mining classification techniques, including support vector machine, random forest, multivariate adaptive regression splines, extreme learning machine, and extreme gradient boosting. In total, 4,287 patients in the datasets provided by three hospital tumor registries were used. Our empirical results revealed that this proposed predictive scheme provided promising classification results and the identification of important risk factors for predicting second colorectal cancer based on accuracy, sensitivity, specificity, and area under the curve metrics. Collectively, our clinical findings suggested that the most important risk factors were the combined stage, age at diagnosis, BMI, surgical margins of the primary site, tumor size, sex, regional lymph nodes positive, grade/differentiation, primary site, and drinking behavior. Accordingly, these risk factors should be monitored for the early detection of second primary tumors in order to improve treatment and intervention strategies.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been found to be modulators of immune function. Additionally, they may affect the growth of colorectal cancer (CRC). With the advent of novel treatment approaches in oncology targeting immune checkpoint inhibition and aiming to boost the immune response against tumors the exact role of n-3 and n-6 PUFA in inflammation as well as in CRC needs to be re-evaluated in order to understand potential interactions with these new treatment paradigms. Interestingly, for the cyclooxygenase (COX) inhibitor aspirin a possible synergistic effect together with a PD1-Ligand antibody has been shown. However, could n-3 PUFA be disadvantageous in the context of immune tumor therapy due to an immune suppressive effect that has been described for these fatty acids in the past, or could they also enhance the effect of immune checkpoint inhibition? In this paper, we discuss the current data regarding the immune modulatory as well as the anti-CRC effect of n-3 PUFA. Arguing towards an immune-activating effect of n-3 PUFA, we demonstrate the results of a pilot study. Here, we show that incubation of human peripheral blood mononuclear cells (PBMCs) with the n-3 PUFA docosahexaenoic acid (DHA) significantly decreases CRC-cell supernatant-triggered secretion of IL-10 and increases secretion of TNF-a, while the omega-6 polyunsaturated fatty acid (n-6 PUFA) arachidonic acid (AA) reduced TNF-a secretion. These changes in cytokine secretion upon incubation with DHA demonstrate a possible enhancing effect of n-3 PUFA on an anti-tumor immune response.

With advances in next-generation sequencing(NGS) technologies, large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer mechanism is to identify the driver genes from the mutation genes by analyzing and integrating multi-types genomics data. Breast cancer is known as a heterogeneous disease. The identification of subtype-specific driver genes is critical to guide the diagnosis, assessment of prognosis and treatment of breast cancer. We developed an integrated frame based on gene expression profilings and copy number variation(CNV) data to identify breast cancer subtype-specific driver genes. In this frame, we employed statistical machine-learning method to select gene subsets and utilized an module-network analysis method to identify potential candidate driver genes. The final subtype-specific driver genes were acquired by paired-wise comparison in subtypes. To validate specificity of the driver genes, the gene expression data of these genes were applied to classify the patient samples with 10-fold cross validation and the enrichment analysis were also conducted on the identified driver genes. The experimental results show that the proposed integrative method can identify the potential driver genes and the classifier with these genes acquired better performance than with genes identified by other methods.

There are many molecules used as drug carrier. TUD-1 is a newly synthesized mesoporous silica (SM) molecule possess two important features; consists of mesoporous so it is very suitable to be drug carrier in addition to that it has the ability to induce apoptosis in cancer cells. However, the effect of TUD-1 appears to act as cell death inducer, regardless of whether it is necrosis or apoptosis. Unfortunately, recent studies indicate that a proportion of cells undergo necrosis rather than apoptosis, which limits the use of TUD-1 as a secure treatment. On the other hand, lithium considered as necrosis inhibitor element. Hence, current study based on the idea of production a new Li/TUD-1 by incorporated mesoporous silica (TUD-1 type) with lithium in order to produce a new compound that has the ability to activate apoptosis by mesoporous silica (TUD-1 type) and at the same time can inhibit the activity of necrosis by lithium. Herein, lithium was incorporated in TUD-1 mesoporous silica by using sol-gel technique in one step synthesis procedure. Moreover, lithium was incorporated in TUD-1 with different loading in order to form different active sites such as isolated lithium ions, nanoparticles of Li2O, and bulky crystals of Li2O. The ability of the new compounds to induce apoptosis and prevent necrosis was evaluated on three different types of cancer cell lines which are; liver HepG-2, Breast MCF-7 and colon HCT116. The obtained results show that Li/TUD-1has the ability to control necrosis and thus reduce the side effects of treatments containing silica in the case of lithium has been added to them, especially in chronic cases. This has been demonstrated by the significant increase in the IC50 value and cell viability comparing to control groups. Consequently, the idea is new, so it definitely needs more develop and test with materials that have more apoptotic impact than silica in order to induce apoptosis without induction of necrosis.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p&lt;0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

This is growing recognition of early onset gastrointestinal (GI) malignancies in young adults

Background: The present study investigated the effects of a micronutrient combination with proven impact on prostate cell metabolism and growth with regard to PSA dynamics. Methods: In an open single-arm multicenter study, 46 men with different baseline situations were recruited: 16 men with constantly elevated PSA values and negative prostate biopsy (group A), and 30 men with low risk prostate cancer on Active Surveillance (Group B) Results: In group A, 12 out of 16 men (75%) showed a decrease of PSA after 6 months from an average 9.26 to an average 8.84 ng/ml (4.5%), whereas in group B, PSA level decreased in 16, increased in 12 men, and remained unchanged in 1 man. The average PSA in group B dropped from 7.47 to 6.82 ng/ml (8.6%).Both PSA decreases were not statistically significant. Conclusion: The results of the present study are consistent with previous findings on the positive effects of individual micronutrients on prostate health. Longer administration of micronutrients or different dosage or combinations may further improve PSA outcomes.

Histone Deacetylase 6 (HDAC6) is a large multidomain protein that deacetylates lysine residues on cytoplasmic proteins, influencing a wide range of cellular processes. Both the catalytic and non-catalytic functions of HDAC6 are implicated in cancer development and progression. Over a decade of clinical trials with catalytic domain inhibitors, such as Ricolinostat (ACY1215), has shown that these drugs are well tolerated and can alleviate chemotherapy-induced peripheral neuropathies. However, their effectiveness in treating solid tumors remains uncertain due to the limited number of clinical trials and the small size of patient cohorts, leading to inconclusive results. HDAC6 activity is regulated by protein-protein interactions and post-translational modifications, which may allosterically influence its catalytic domains. Therefore, targeting HDAC6 in cancer therapy with small molecule inhibitors requires a more sophisticated understanding of its role within the tumor microenvironment, including whether its expression correlates with deacetylase activity. A comprehensive evaluation of both its enzymatic and non-enzymatic functions could be crucial in developing more effective strategies for targeting HDAC6 in cancer.

Tumor entities of the Central Nervous System (CNS) are defined by the WHO classification and range from benign neoplasms to highly malignant tumors, making histopathological classification challenging. This diverse spectrum complicates clinical decision-making and the interpretation and validation of clinical trial results. The methodology based on DNA methylation profiling of CNS tumors offers greater diagnostic precision compared to traditional morphological methods. In this study, we analyzed 16 DNA samples from medulloblastomas and ependymomas, obtained from paraffin-embedded blocks from the Pathology Division archives of HCFMUSP, and with prior histological analysis. The samples were processed using the Infinium MethylationEPIC BeadChip (Illumina®) and methylation data analysis tools in R Studio. The data were submitted to the MolecularNeuropathology.org platform for methylation based classification and CNV chart generation. The classifier was consistent with the previous diagnosis in all cases, refining the diagnosis in 54% of cases to subclass, 38% to subtype, and 8% to family. The platform also provided CNV estimates for 87% of cases, revealing crucial information on genetic alterations such as gains, losses, amplifications, and gene fusions. Despite the challenges of implementation within the Brazilian Public Health System (SUS), the results demonstrate the method's robustness and reproducibility, promising invaluable support for precise diagnoses and the development of more effective therapeutic strategies.

Taste and smell disorders can worsen the nutritional status of patients receiving chemotherapy and potentially affect drug treatment. However, there is limited knowledge on antineoplastic agents that induce taste and smell disorders. Therefore, we used the US Food and Drug Administration Adverse Event Reporting System database to analyze the characteristics of patients and antineoplastic agents in relation to taste and smell disorders. No gender differences related to onset of taste and smell disorders were found, whereas older age was identified as a possible risk factor. Among antineoplastic agent classes, protein kinase inhibitors appeared to be particularly likely to induce taste and smell disorders. Cluster analysis and principal component analysis that taste and smell disorders induced by antineoplastic agents are characterized by “disorder of taste/smell” and “decrease/change of taste and smell.” These findings might be useful in selecting drugs for patients experiencing similar side effects.

One of the most prevalent malignancies in males is prostate cancer, which most often metastasizes to the liver, thorax, bone, and local lymph nodes. The current case describes development of cervical lymphadenopathy; which remains a rather rare initial presentation, seen in <0.1% of the patients diagnosed with prostatic carcinoma. The current report describes a 55-year-old man with complaints of lower back pain and swelling on the left side of his neck for the previous two months. Physical examination revealed several swollen cervical lymph nodes that measured 2 cm, were nontender, firm, and adhered to the skin above. A poorly differentiated adenocarcinoma was found during cytological examination of the lymph nodes in the left lower cervical region. Findings from the ensuing Computed Tomography scan pointed to the possibility of spread prostatic cancer. PSA values were determined to be 364.762 ng/ml after additional analysis. The patient was then planned for hormone ablation therapy as per Institute protocol, in view of metastatic prostate cancer. The current report highlights the importance of timely detection of malignancies, particularly those such as Prostate cancer, that are slow growing and have well-established screening tools (such as PSA assays). Involvement of the cervical lymph nodes in prostate cancer, particularly for older individuals, is nearly always linked to extensive metastatic disease. As a result, it is a poor prognostic factor for prostate cancer patients, whose survival rates are markedly lower. Although hormone therapy has advanced significantly as the cornerstone of care for metastatic prostate cancer, the prognosis for these cases is still quite poor, especially when there has been distant lymph node metastases.

Elevated resting heart rate is frequently observed in cancer patients, and is associated with increased mortality. Although specific chemotherapeutic agents can induce cardiotoxicity, the presence of sinus tachycardia in chemotherapy-naive patients suggests other factors likely contribute to this clinical presentation. Despite its prevalence, cancer-associated resting sinus tachycardia has not been fully recognized and comprehensively described as a separate clinical entity. Secondary effects of cancer, especially structural cardiac changes, secretory factors (inflammatory cytokines), and thromboembolic disease can cause resting tachycardia. Alternatively, rapid heart rate may reflect compensatory mechanisms responding to increased metabolic demands, raised cardiac output states, and even pain. Hence, cancer-associated tachycardia presents a clinical dilemma; acute life-threatening conditions (such as sepsis, pulmonary embolism, etc.) must be ruled out, but cancer itself can explain resting sinus tachycardia and more conservative management can avoid unnecessary testing, cost and patient stress. Furthermore, identification and management of cardiac conditions associated with cancer may improve survival and the quality of life of cancer patients.

Prostate cancer, according to the World Health Organization (WHO), ranks as the fourth most prevalent type in the population, even though it is highly frequent when detected early and promptly treated, resulting in a low mortality rate. However, in some cases, despite adherence to proper clinical protocols, there is a progression to castration-resistant prostate cancer (CRPC). In these cases, as outlined in clinical guidelines such as those developed by the National Comprehensive Cancer Network (NCCN), one approach involves the utilization of the pharmaceutical agent abiraterone to implement androgen deprivation therapy (ADT), aimed at suppressing the production of hormones directly implicated in disease progression. Another noteworthy aspect is the limited literature on clinical protocols and their efficacy concerning the Amazonian indigenous population, which often exhibits unique genomic profiles, with descriptions of variants not yet documented in the literature. Building upon these considerations, this study aims to survey the variants identified in genes associated with the abiraterone signaling pathway, their frequencies in the Amazonian indigenous population, and the correlation of these frequencies with those observed in other global populations. The objective is to contribute to the refinement of clinical practices in the treatment of prostate cancer within this population.

Metastatic melanoma patients have a poor prognosis with poor responsiveness to chemotherapy. BRAF V600E mutations have been detected in ~40% of melanoma patients. Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma, which already presents resistance that leads to patient relapse and the serious side effects. In our study, we synthesized 5 new vemurafenib analogs, RF-86A, RF-87A, RF-94A, RF-94B and RF-96B, with structural improve-ments, in order to increase the anti-proliferative and anti-metastatic effect on human melanoma. We showed that the analogs were efficient in inducing cell death and reducing the migration of A375 cells, by inhibition of MMP-2 and MMP-9 activity, indicating that this action may be longer lasting comparing to the action of Vemurafenib.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Background: Orthostatic hypotension (OH) is associated with higher risk of mortality in general population however not studied in cancer population. The study aimed to assess the prevalence of OH in cancer patients compared to the non-cancer population. Methods: A total of 411 patients (mean age 63.5 ± 10.6 years) were recruited: patients with active cancer (n = 223) and patients hospitalized for other reasons but without cancer diagnosis (n = 188). Medical history was collected and an orthostatic challenge test was performed. OH was defined as blood pressure (BP) decrease on standing ≥ 20 mmHg for systolic or ≥ 10 mmHg for diastolic BP in 1 or 3 minutes; or systolic BP decrease &lt; 90 mmHg. Results: The prevalence of OH in cancer was significantly higher than in subjects without cancer- 28.7% vs. 16.5%, respectively, P = 0.003). OH was the most common in lung cancer, 57.5%. In single variable analysis, the predictors of OH were: cancer presence, age ≥ 65 years, and body mass index (BMI) ≥ 30 kg/m2. In the multivariable model, the strongest independent predictor of OH was cancer status doubling the risk of OH; BMI ≥ 30 kg/m2 and diabetes. Conclusions: Cancer patients are characterized by a high prevalence of OH. In this population, the recommendation of routine orthostatic challenge tests should be considered.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Background and Objectives: The purpose of the study was to analyze the relationships between several clinical and biological factors, but also the tumor topography and surgical strategies used in patients with colorectal cancer. Materials and Methods: We designed an analytical, observational, retrospective study that included patients admitted to our emergency surgical department and diagnosed with colorectal cancer. The study group inclusion criteria were: patients admitted during 2020-2022; patients diagnosed with colorectal cancer (including the ileocecal valve); patients who benefited from a surgical procedure, either in emergency or elective. Results: In our study group, consisting of 153 patients, we accounted for 56.9% male patients and 43.1% female patients. The most common clinical manifestations were pain (73.2% of the study group), followed by abdominal distension (69.3% of the study group) and absence of intestinal transit (38.6% of the study group). A number of 69 patients were operated in emergency (45.1%), while 84 patients (54.9%) benefited from elective surgery. The most frequent topography of the tumor was the sigmoid colon, with 19.60% of the patients, followed by the colorectal junction, with 15.68% of the patients and superior rectum and inferior rectum, with 11.11% of the patients in each subcategory. The most frequent type of procedure was right hemicolectomy (21.6% of the study group), followed by rectosigmoid resection (20.9% of the study group). The surgical procedure was finished by performing an anastomosis in 49% of the patients, an ostomy in 43.1% of the patients, while for 7.8% of the patients, a tumoral biopsy was performed. Conclusions: Colorectal cancer remains one of the most frequent cancers in the world, with a heavy burden that involves high mortality, alterations in the quality of life of the patients and their families, and also the financial costs of the medical systems.

Nanotechnology has provided an opportunity for unparalleled development of the treatment of various severe diseases. The unique properties of nanoparticles offer a promising strategy in enhancing antitumor immunity by enhancing immunogenicity and presentation of tumor autoantigens for cancer immunotherapy. Polymeric, liposomal, carbon or silica-based nanoparticles are among those with major immunomodulatory roles in various cancer treatments. Cancer vaccines, in particular digestive cancer vaccines have been researched and developed on nanotechnological platforms. Due to their safety, controlled release, targeting of dendritic cells(DCs) and improved antigen uptake, as well as enhanced immunogenicity, nanoparticles have been used as carriers, as adjuvants for increased effect at the tumor level, for their immunomodulating effect, or for targeting tumor microenvironment, increasing tumor immunogenicity and reducing tumor inflamatory response. This review looks at digestive cancer vaccines developed on nanoparticle platforms and the impact nanoparticles have on the effects of these vaccines.

Gut microbiota composition can affect tumor microenvironment and its interaction with the immune system, thereby having implications on treatment predictions. This article reviews the studies available to better understand how gut microbiomes help the immune system to fight cancer. To describe this fact, different mechanisms, and approaches of utilizing probiotics to improve advancements in cancer treatment will be discussed. Moreover, not only the calorie intake but also the variety and quality of diet can influence cancer patient’s immunotherapy treatment because dietary patterns could impair the immunological activities either by stimulating or suppressing the innate and adaptive immunity. Therefore, it is interesting and critical to understand the gut microbiome composition as a biomarker to decide cancer immunotherapy outcomes and responses. Here, more emphasis would be given to the recent development in immunotherapies utilizing microbiota to improve cancer therapies which is beneficial for cancer patients.

The emergence of bispecific antibodies has transformed cancer immunotherapy, highlighting increased clinical efficacy, especially in hematological malignancies. These innovative molecules uniquely target two distinct tumor antigens or separate epitopes simultaneously, demonstrating potent antitumor activity across various cancers. Despite their promise, challenges like rapid drug clearance, off-target effects, and cytokine release syndrome hinder their widespread therapeutic application. Recent engineering advancements in bispecific antibody systems aim to overcome these challenges, broadening therapeutic coverage. This review offers insights into the latest clinical and preclinical progress in bispecific immunotherapy, outlining key challenges faced by the technique, and exploring emerging strategies to address these obstacles.

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10^-5, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10^-4 or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse.

Background: Although previous studies have implicated a role for the stool microbiome in cancer cachexia, the fecal microbiome has not been previously characterized for patients with pancreatic ductal adenocarcinoma (PDAC) and cachexia treated with nutritional interventions such as enteral feeding. Methods: The PANCAX-1 (NCT02400398) prospective trial enrolled 31 cachectic advanced PDAC patients to receive jejunal tube peptide-based diet for 12 weeks who were planned for palliative chemotherapy. Out of 16 evaluable patients, 62.5% receiving enteral feeding met the primary endpoint of weight stability at 12 weeks. As part of an exploratory analysis of the PANCAX-1 trial, serial stool and blood samples were collected at 0 (C1D1), 6 (C2D1), and 12 (C3D1) weeks over the 12-week period of enteral feeding. Stool samples were analyzed using 16S v4 sequencing of the microbiome. Up to 219 plasma metabolites were analyzed by mass spectrometry and high-performance liquid chromatography. Results: A total of 29 stool samples were prospectively collected from 16 subjects with PDAC enrolled in PANCAX-1 who were evaluable for weight stability. Over 12 weeks of enteral feeding, statistically significant increases in the abundance of bacterial genera such as Veillonella (p=0.0150) and Actinomyces (p=0.0390) were observed, while there was a lower abundance of Bacteroides (p=0.0150) and Butyricicoccus (p=0.0390). Greater abundance of Veillonella and reduced Bifidobacterium at baseline were linked to greater weight stability. Plasma metabolomics in 10 subjects showed that weight unstable patients had significantly decreased levels of essential (L-histidine, L-phenylalanine) and non-essential amino acids (L-citrulline, L-tyrosine, all p<0.05) at the end of 12 weeks of enteral feeding. High stool Veillonella abundance was significantly associated with increases in the nucleotide 2-deoxycytidine 5-diphosphate and essential amino acid L-isoleucine but decreased TCA cycle metabolite alpha-ketoglutarate (all p<0.05). Conclusions: We are the first to demonstrate the feasibility of stool microbiome profiling and plasma metabolomics in paired stool and plasma samples from a prospective cohort of advanced PDAC patients on enteral feeding as their primary source of nutrition. Our findings are hypothesis-generating in that metabolites unique to weight stability and abundance of stool bacterial genera may inform future studies of anti-cachexia therapies involving enteral feeding or microbial modulation.

Cancer have been known as a most important global mortality reason, which in spite of novel therapeutic ways, the leading death is still considerable. Molecular targeted diagnosis and therapy using aptamers with high affinity have converted to a popular technique for pathological angiogenesis and cancer therapy scientists. In this paper several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently) and biosensors, which successfully designed for biomarkers, are critically reviewed. The results obviously demonstrated that aptamer have potentially incorporated with targeted delivery systems and biosensors for detection of biomarkers which expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, as the main field of medical sciences, possess high potential in cancer therapy, pathological angiogenesis and increase of community health. The clinical use of aptamer is so limited due to unreliability resulted from targets impurities, inaccuracy in SELEX stages process, and in vitro synthesis which led to the lower selectivity for in vivo targets. Moreover, size behavior, probable toxicity, low-distribution and unpredictable behavior of nanomaterials in in vivo media make critical their usage in clinical assays. This review can be helpful for implementation and designing the future studies which are effective and applicable for clinical use.

Human urinary bladder cancer has similar development that invasive urothelial cancer that happens spontaneously in dogs. Then, research of these malignant tumors associated with the advances of new treatment drive to the specific fight of the urothelial tumor cell, is highly valuably related to efficiency and reduction of side effects of treatments, even extrapolating to humans. Thus, a review of the most important aspects on new advances on canine bladder cancer was achieved. Many forms of therapies are being reported; one of them, of highly promising feature is the treatment with immunomodulators. The resemblance between spontaneous urothelial cancer in canines and urinary bladder cancer in humans makes this canine tumor relevant animal model to research and advances of treatment that may be more efficient in management of tumor with less unfavorable effects. Immunomodulators exhibit important outcomes when used in the therapy of bladder cancer in dogs. Nanomaterials that are possible carriers of some kinds of drugs to the target tumor significantly raise the efficiently of the therapy. Therefore, the advancement of immunomodulator combined with nanoparticles can disrupt the therapy of bladder cancer in dogs and thereafter in humans.

(1) Background: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; (2) Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; (3) Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, P < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, P < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, P < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, P < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, P < 0.05). The increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, P < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, P = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, P = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, P = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, P < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, P < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, P < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, P < 0.01). Furthermore, increased HER-2 expression is an independent risk factor for recurrence-free survival (RFS) in patients (P < 0.01, HR = 3.421); (4) Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

The search for more efficacy and fewer toxic effects in cancer treatments is the main objective of research into new therapies. Vincristine (VCR) is a chemotherapeutic used in different types of tumors. Epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in different investigations, so the objective of this work was to evaluate the antitumor effect of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG and their combination; Tumor grow and survival time were recorded. Once the tumors were obtained, they were measured and immunohistochemistry was performed for p53, Bcl2 and CD1. The results showed that the EGCG/vincristine combination had a greater antitumor effect that vincristine and EGCG. This can be partly attributed to the fact that the greatest Bcl2 inhibition was present in the combination of EGCG with vincristine. Therefore, it can be concluded that the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival than both substances independently.

The Myc gene, widely studied in numerous cancer types, serves as a pivotal regulator of crucial cellular processes implicated in tumorigenesis, such as cell growth, proliferation, invasion, metastasis, and therapy resistance. LncRNAs have been identified as relevant partners of Myc. LncRNAs modulate chromatin structure and function, transcription, splicing, stability, and translation of mRNAs, thereby emerging as pivotal regulators in cell differentiation, metabolism, signaling. An intricate crosstalk exists between Myc and lncRNAs in a wide range of cancers, wherein they can physically and functionally interact through direct and indirect mechanisms. Some lncRNAs can regulate Myc activity at post-transcriptional level, affecting its stability, translation, or interactions with other proteins, thus acting as oncogenes, while others act as tumor suppressors. On the other hand, Myc can target numerous lncRNA genes and modulate their expression, affecting the expression of downstream targets involved in tumorigenesis. Given the significant role of the Myc-lncRNA network in various cancer types, exploring therapeutic strategies targeting these crucial cellular regulators is of utmost importance. This review article focuses on breast cancer, analyzing those lncRNAs influencing Myc as well as the Myc-regulated lncRNAs.

Background: Wilms' tumor (or nephroblastoma) is a malignant and solid neoplasm that derives from the primitive renal bud. It represents the most frequent primary tumor of the urogenital tract in childhood, and treatment consists of surgery and chemo-radiotherapy. However, concerning the quality of life, the new therapeutic frontier is exploring other safer and potentially more effective options, such as minimally invasive surgery and biological drugs. Method: Literature (Pubmed) from January 2013 to March 2023 was reviewed. Results: One hundred five articles were included in the review. Conclusion: In addition to the therapeutic strategies already identified, such as classic surgery and pharmacological therapies, recent studies focus attention on the new frontiers of minimally invasive surgery, such as diagnostics using biomarkers and immunotherapy, which could represent a new therapeutic option and possibly less risky than in the past, contributing in fact to the current knowledge of the scientific panorama in terms of "tumor microenvironment" and systemic implications deriving from oncological disease.

Colon cancer (CC) is one of the leading causes of cancer-related death worldwide. Gene hypermethylation is a well-known alteration that contributes to tumour progression in CC. It is essential to analyse new molecular markers that can delineate more aggressive CC cases. The detection of new epigenetic alterations such as hypermethylation and hypomethylation of regulatory gene regions that participate in crucial mechanisms of cancer progression, such as epithelial mesenchymal transition (EMT), could be useful for identifying cases that might benefit from a closer follow-up by clinicians. In the present report we describe, for the first time, the hypermethylation of the ZEB1 gene, which is more frequent in cases without expression of hMLH1. More importantly, this epigenetic alteration is a good prognostic factor related to disease-free and overall survival in all cases and Consensus Molecular Subtypes (CMS2/3) independently of other clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasion.

Abstract: In the last decade, gypsogenin has widely grabbed the attention of medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin proved itself as a new an-ti-proliferative player battling for a front position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospect rational design. The present article opens a new venue for better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

Probiotics are now being looked at as a possible addition to cancer treatments in both study and clinical settings. This study tries to give an overview of probiotic research as it relates to cancer, with a focus on how it might help avoid cancer, treat it, and improve the health of cancer patients. We look at developmental studies that use cell culture and animal models to look at how well probiotics work in cancer. We focus on how probiotics change the immune system, inflammation, and gut bacteria. The results of clinical studies that looked at probiotics as an add-on therapy for cancer patients are looked at to see how they affected the treatment success, side effects, and quality of life of the patients. We look at the possible benefits of probiotics for certain types of cancer, such as colorectal cancer, breast cancer, and stomach tumors. We also find the best probiotic strains for each type of cancer. We also look at the synergistic benefits of combining probiotics with standard cancer treatments like chemotherapy, radiation therapy, and immunotherapy to improve the effectiveness of treatment and lower side effects. Lastly, we talk about the present problems and future directions of probiotic research for cancer. We focus on personalized methods, ideal doses and treatment plans, finding signs of treatment success, and making probiotic-based therapies. By learning more about how probiotics could be used to treat cancer, we can create personalized, successful, and well-tolerated probiotic treatments to improve cancer outcomes.

Major limitations in the effective treatment of neurological cancer include systemic cytotoxicity of chemotherapy, inaccessibility, and inoperability. The capability to successfully target a drug to the tumor site(s), without incurring serious side effects, especially in the case of aggressive tumors, such as glioblastoma and neuroblastoma, would represent a significant breakthrough in therapy. Orthotopic systems, capable of storing and releasing proteins over a prolonged period at the site of a tumor, utilising nanoparticles, liposomes, and hydrogels have been proposed. One candidate for drug delivery is Micro-Fragmented Adipose Tissue (MFAT). Obtained easily from the patient by abdominal subcutaneous liposuction (autologous), and with a high content of Mesenchymal Stem Cells (MSC), mechanically derived nanofat is a natural tissue graft with a structural scaffold organization. It has a well preserved stromal vascular fraction, and a prolonged capacity to secrete anti-tumorigenic concentrations of pre-absorbed chemotherapeutics within extracellular vesicles. This review discusses current evidence supporting the potential of drug modified MFAT for the treatment of neurological cancer with respect to recent preclinical and in vitro studies. Possible limitations and future perspectives are considered.

Objective: to create a set of eligibility criteria for the use of MHT in non-gynecological cancer patients. Methods: We searched all articles published in peer-reviewed journals up to March 2021. The PICOS standards were used and the selection criteria as follows: menopausal women of any age with non-gynecological and non-breast cancer receiving HMT, any MHT preparation (oestrogens alone or combined with a progestogen, tibolone or tissue selective oestrogen complex) or any route of administration (oral, transdermal, vaginal or intra-nasal), recurrence and mortality, randomized controlled trials, and related extension studies or follow-up reports. Results: Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women Skin Melanoma Survivors Using MHT Have Longer Survival than Non-MHT Survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rates than those survivors who do not use MHT. Conclusion: MHT is safe in women who have suffered from colorectal, lung or skin melanoma cancers The study was registered at www.prospero.org (CRD42020166658)

Tissue inhibitors of metalloproteinases (TIMPs) are essential players during tumor progression in various types of cancer, including breast cancer. TIMPs regulate the activity of matrix metallo-proteinases (MMPs) at different levels. However, a dual role for TIMPs in breast carcinogenesis, either promoting or inhibiting tumor progression, has been observed. By a comprehensive bioin-formatics analysis using different databases, we report that of the four TIMPs, only TIMP-1 is overexpressed in tumor breast tissue. However, TIMP-2, TIMP-3, and especially TIMP-4 present lower levels in breast tumor tissue than in normal tissue. Interestingly, high levels of TIMP-1 are associated with shorter survival in breast cancer patients. In contrast, low TIMP-2, TIMP-3, and TIMP-4 levels are associated with poor survival. Function enrichment analysis showed that TIMP-3 has the highest interactions with its target proteins and a higher number of processes re-lated to mammary carcinogenesis. We found differential expression of TIMP-1 concerning TIMP-3 and TIMP-4 in breast cancer and normal tissue. TIMP-4 has a significant relationship with cancer staging, including tumor size, lymph node spread, and metastasis. The correlation between immune cell infiltrates and TIMP expression is of great importance as they provide in-formation on breast cancer diagnosis, prognosis, progression, and response to treatment.

Claudin-18.2 (CLDN18.2) is specifically expressed in pancreatic precancerous lesions and pancreatic ductal adenocarcinoma (PDAC). We assessed clinical characteristics of patients with CLDN18.2 overexpressing pancreatic cancer to identify patients who might benefit from CLDN18 targeted treatment. 130 patients with surgically resected PDAC were investigated the immunohistochemical expression of claudin-18 (CLDN18). The CLDN18 staining intensities (0-3+) and relative proportion of positive tumor cells were analyzed by two independent raters. Tumor as positive for CLDN18 expression was defined as ≥80% of tumor cells with 2+ or 3+ staining intensity on CLDN18 immunohistochemical assay. Positive CLDN18 expression was present in 41/130 (31.5%) surgically resected PDAC and the relative proportion of positive tumor cells and the staining intensity were directly correlated (p &lt; 0.001). Positive CLDN18 expression was significantly associated with well-differentiated tumor (p&lt;0.001) and less regional node involvement (p=0.045). The positive CLDN18 expressing group showed no statistical difference in median overall survival (17.4 months vs. 20.6 months, p=0.770) compared to negative CLDN18 expressing group. Distant nodal metastasis was more frequent in positive CLDN18 expressing group (p=0.011). CLDN18 is frequently expressed in PDAC, and high CLDN18 expressing PDAC showed some different clinicopathologic characteristics. High CLDN18 expression was not associated with prognosis in patients with surgically resected PDAC.

Currently, there are many studies on the application of nanotechnology in therapy. Metallic nanoparticles are promising nanomaterials in cancer therapy, however, functionalization of these nanoparticles with biomolecules has become relevant as their effect on cancer cells is con-siderably increased by photothermal and photodynamic therapy, drug nanocarriers, and speci-ficity by antibodies, resulting in new therapies that are more specific against different types of cancer. This review describes studies on the effect of functionalized palladium, gold, silver and platinum nanoparticles in the treatment of cancer.